# Systematic screening for new histone marks and studying their epigenetic function

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2022 · $508,853

## Abstract

Epigenetic regulation is critical to diverse biological processes and diseases. Post-translational
modifications (PTMs) in histones are generally considered to be a major group of epigenetic marks,
contributing to the epigenetic program that dictates diverse DNA-templated biological outputs. Our team has
recently identified nine types of novel histone PTMs (lysine propionylation, lysine butyrylation, lysine
malonylation, lysine succinylation, lysine glutarylation, lysine crotonylation, lysine 2-hydroxyisobutyrylation,
lysine 3-hydroxybutyrylation, and lysine benzoylation). Importantly, we and others demonstrated critical roles
for these new PTM pathways by revealing their unique functions in the transcriptional control of gene
expression and cellular regulation, and by linking them to multiple inborn metabolic diseases. Some of these
histone marks can be stimulated by cellular levels of their corresponding short-chain lipids, thus suggesting
new mechanisms for metabolism-regulated epigenetic changes. This application is based on the tremendous
expertise we gained during our earlier studies on identification and characterization of nine novel types of
histone marks. We hypothesize that additional, undescribed types of histone PTMs are present in mammalian
histones. Our hypothesis is supported by our preliminary data identifying multiple undescribed PTMs in
histones, the chemical structures of which are either undefined or remain to be fully validated. We propose to
use an integrated approach, employing technologies that have been well established and fully validated in the
laboratories of our team, to comprehensively screen for novel types of histone PTMs. Our team is best
positioned to find these histone marks because of the tremendous skills and numerous technologies we have
accumulated, and the high productivity we have demonstrated in our recent identification of the novel types of
histone marks. We will first comprehensively screen for new types of histone marks and validate them by both
chemical and biochemical methods. We will then investigate their epigenetic roles during spermatogenesis.
New types of histone marks will significantly advance our understanding of chromatin structure and function,
might open unforeseen avenues for epigenetic studies, and may even shift the focus of current research on
epigenetic mechanisms and disease.

## Key facts

- **NIH application ID:** 10401345
- **Project number:** 5R01GM135504-03
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** YINGMING ZHAO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $508,853
- **Award type:** 5
- **Project period:** 2020-03-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401345

## Citation

> US National Institutes of Health, RePORTER application 10401345, Systematic screening for new histone marks and studying their epigenetic function (5R01GM135504-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401345. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*